Prudhomme S, Bonnaud B, Mallet F
UMR 2142 CNRS-bioMérieux, IFR 128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon, France.
Cytogenet Genome Res. 2005;110(1-4):353-64. doi: 10.1159/000084967.
Endogenous retroviruses (ERV), as part of the host genetic heritage, are transmissible to the next generation in a Mendelian way. Their abundance in animal genomes and their expression primarily detected in germ cells, embryonic tissues and cancer cell lines, raised the question of their biological significance. This article reviews the possible role of ERVs in the physiology and diseases of animal reproduction, from Drosophila to human. In males, there is no trivial involvement of ERVs in a physiological process. Conversely, a spermatogenesis defect was associated in the human male with HERV-K expression and HERV15-induced chromosomal alteration, leading to cancer and infertility, respectively. In females, the study of insect ERVs (IERV) pointed out the overlap between genetics and virology with the genetic-dependent regulation of ZAM and the non-infectious and infectious life cycles of gypsy. The pattern of ERVs expression in rodent, ovine and human females suggest a hormone-dependent mechanism consistent with the mammalian oestrus cycle regulation. The differentiation of the mammary epithelium and breast tumorigenesis involving the mouse mammary tumour viruses (MMTV) illustrate the intimate connection between endogenous and exogenous retroviruses. Last, as a major site of ERVs transcription, placenta contributed to our understanding of ERVs modulation of neighbouring gene expression. As an interface, i.e. a site of conflicts and exchanges, placenta should resist infection and protect the foetus against the maternal immune system. Retroviral envelopes could theoretically provide such features due to receptor interference, immunosuppression and fusion properties, as shown by the HERV-W envelope involved in the syncytiotrophoblast formation. We conclude with an insight on the evolutionary and epigenetic consequences of the relationships of ERV guests with their animal hosts.
内源性逆转录病毒(ERV)作为宿主遗传遗产的一部分,能够以孟德尔方式传递给下一代。它们在动物基因组中数量丰富,且主要在生殖细胞、胚胎组织和癌细胞系中表达,这引发了对其生物学意义的质疑。本文综述了ERVs在从果蝇到人类的动物生殖生理和疾病中的可能作用。在雄性动物中,ERVs在生理过程中并非微不足道。相反,在人类男性中,精子发生缺陷与HERV-K表达以及HERV15诱导的染色体改变有关,分别导致癌症和不育。在雌性动物中,对昆虫ERVs(IERV)的研究指出了遗传学和病毒学之间的重叠,即ZAM的遗传依赖性调控以及吉普赛病毒的非感染性和感染性生命周期。ERVs在啮齿动物、绵羊和人类雌性中的表达模式表明存在一种与哺乳动物发情周期调节一致的激素依赖性机制。涉及小鼠乳腺肿瘤病毒(MMTV)的乳腺上皮细胞分化和乳腺肿瘤发生说明了内源性和外源性逆转录病毒之间的密切联系。最后,作为ERVs转录的主要部位,胎盘有助于我们理解ERVs对邻近基因表达的调节。作为一个界面,即冲突和交换的场所,胎盘应抵抗感染并保护胎儿免受母体免疫系统的影响。理论上,逆转录病毒包膜可由于受体干扰、免疫抑制和融合特性而提供这些功能,如参与合体滋养层形成的HERV-W包膜所示。我们最后深入探讨了ERV宿主与其动物宿主关系的进化和表观遗传学后果。